Subchronic arsenic toxicity in rats

Environ Toxicol. 2010 Aug 19. [Epub ahead of print]

Pathological, immunological and biochemical markers of subchronic arsenic toxicity in rats

Nain S, Smits JE.

Ecosystem & Public Health, Faculty of Veterinary Medicine, University of Calgary, Calgary, Alberta, Canada T2N 4Z6.

Abstract

Subchronic exposure to arsenic in rats was investigated to identify sensitive indicators of subclinical toxicity in rats. Immunological, pathological, and biochemical bioindicators were examined in rats exposed to arsenic in their drinking water. Juvenile male Wistar rats were allocated to four treatment groups receiving 0, 0.4, 4, and 40 ppm of arsenite in drinking water for 18 wks. Besides daily monitoring for clinical signs of adverse health effects, clinical biochemistry, B-cell-mediated and innate immune responses, plus gross, and histopathology were examined. In vitro tests of oxidative damage to basic cellular constituents, lipids, proteins, and nucleic acids, were measured using thiobarbituric acid reacting substances (TBARS) assays, protein carbonyl formation, and 8-hydroxydeoxyguanosine (8-OHdG), respectively. Clinical changes in the rats were limited to decreased feed and water intake in the high- (40 ppm) dose group (P < 0.05), however, growth rate was not affected. Serum biochemical changes occurred in blood urea nitrogen, K(+), Cl(-), and alanine aminotransferase (ALT) from arsenic exposure. Immunotoxicity was evident through a dose-dependent suppression of the secondary antibody-mediated response to a T-cell-dependent antigen, keyhole limpet hemocyanin (KLH). Histopathology of the liver revealed marked fatty infiltration and vacuolization particularly evident in periacinar hepatocytes. This pattern of toxicopathology in the high-exposure group may be related to the significantly higher (P < 0.05) oxidative stress, demonstrated through lipid peroxidation (TBARS assay) in the rats exposed to 40 ppm arsenite. The present study revealed that young, growing rats exposed to arsenic for 18 wks tolerated exposures up to 4 ppm. At higher doses, there was evidence of hepatotoxicity, humoral immunity was compromised, and an adverse effect on hepatic organelle and cell membranes was evident through a dose dependent increased in oxidative stress. (c) 2010 Wiley Periodicals, Inc. Environ Toxicol, 2010.